Hormones and Calcium Homeostasis

Key Hormones Influencing Animal Homeostasis

Overview of Today's Discussion

  • Focus: Hormones influencing calcium homeostasis.
  • Calcium significance in physiological processes will be covered.
  • Key regulators: Thyroid and parathyroid hormones.
  • Vitamin D: Peripheral involvement in calcium homeostasis.
  • Mention of metabolic disorder (milk fever).

Plan for Tomorrow

  • Cell signaling lecture: Linking hormones and cellular changes (including metabolism).
  • Quick summary of endocrine components.
  • Final exam discussion and case studies.

Hormones of the Thyroid and Parathyroid

  • Parathyroid hormone.
  • Calcitonin (thyrocalcitonin).
  • Vitamin D.
  • Source and roles of calcium.

Dysregulation Example: Milk Fever

  • Metabolic disorder in cattle (especially dairy) and sometimes dogs.
  • Occurs post-parturition or during lactation.
  • Symptoms: Recumbency (lying down, unable to get up).
  • Cause: Calcium dysregulation (hypocalcemia).
  • Treatment: Intravenous calcium administration (into the milk vein).
  • Rapid recovery after calcium administration, demonstrating the importance of calcium.

Calcium Homeostasis: Key Regulators

  • Parathyroid Hormone.
  • Calcitonin.
  • Vitamin D.

Significance of Calcium

  • About 1% of total body weight.
  • Mainly as hydroxyapatite in bones (calcium phosphate).

Calcium Distribution

  • 99% in bones as hydroxyapatite.
  • Small amount in intracellular soft tissues.
  • Small amount extracellularly.
  • Bones act as a huge reservoir.

Calcium Regulation

  • Calcium levels are closely managed in circulation and within cells due to its significant roles in normal physiology.

Roles of Calcium

  • Muscle Contraction: Facilitates muscle contraction via release from the sarcoplasmic reticulum.
  • Nerve Cell Conduction: Role in setting up membrane potentials for nerve signals.
  • Exocytosis: Signaling role in molecule secretion.
  • Enzyme Kinetics: Influences enzyme conformation through allosteric modifications; acts as a secondary signaler.
  • Cell Membrane Stability: Influences stability.
  • Bone and Teeth: Major component due to the high amount in these tissues.

Regulation Concept

  • Balance between dietary intake, deposition in bone, and excretion from kidneys.

Summary Diagram

  • Parathyroid hormone:
    • Released when calcium levels are low.
    • Effects: bone (mobilize Ca^{2+}), absorption (increase), excretion (reduce).
  • Calcitonin:
    • Secreted when calcium levels are high.
    • Effects: bone (drives Ca^{2+} in), uptake (decrease), loss through kidneys (increase).

Parathyroid Hormone (PTH)

  • Produced by parathyroid glands (small tissues in the neck, co-located with the thyroid).
  • Peptide hormone: 84 amino acids.
  • Quick synthesis and secretion rather than significant storage.
  • Released when calcium concentration declines in circulation.
  • Broken down in liver and kidneys.
  • Short half-life (5-10 minutes) indicating fine regulation.

PTH Secretion Regulation

  • Plasma calcium decline stimulates parathyroid glands to secrete PTH, increasing plasma calcium.
  • Active inhibition: inverse relationship with calcitonin.
  • Secretion is greatest when plasma calcium falls below 1 mM/L.

PTH Effects

  • Increases calcium levels in extracellular fluids (including plasma).
  • Acts on bone, kidneys, and gastrointestinal tract.
    • Low calcium \rightarrow PTH secretion \rightarrow calcium release from bone, absorption increase, excretion decrease.

PTH Effect on Bone

  • PTH has receptors on osteoblasts, stimulating their differentiation into osteoclasts.
  • Osteoclasts reabsorb calcium from bone.
  • Osteoblasts lay down matrix and stimulate calcium absorption into bone.

PTH Effect on Kidneys

  • Increases calcium reabsorption.
  • Stimulates modification of vitamin D in kidneys (important for absorption in the gastrointestinal tract).

PTH Effect on Gastrointestinal Tract

  • Decreased plasma calcium stimulates parathyroid glands \rightarrow PTH release.
  • PTH acts on kidneys \rightarrow increased Ca^{2+} reabsorption and decreased urinary excretion.
  • PTH stimulates modification of vitamin D in the kidneys.
  • Modified vitamin D activates gastrointestinal epithelium to absorb more calcium.

Regulation of PTH Secretion

  • Calcium levels in blood are the primary trigger.
  • Magnesium levels also influence but less pronounced.
  • Diurnal rhythm: elevation during sleep, highest in the morning.

Hyperparathyroidism

  • Oversecretion of PTH.
  • Caused by adenoma (neoplastic growth) in the parathyroid gland.
  • Results in unregulated secretion.
  • Effects: bone resorption, increased absorption in kidneys/gastrointestinal tract, bone morphology changes, fractures, teeth falling out, disrupted neural regulation.
  • Symptoms include gastrointestinal motility changes (vomiting, constipation), depression, muscle weakness.

Hypoparathyroidism

  • Low levels of PTH.
  • Causes: genetic, immune-mediated, idiopathic.
  • Inability to respond to lowering calcium concentrations.
  • Symptoms: uncoordinated gait, muscle tremors/twitching, changes in behavior, seizures, lethargy.

Calcitonin

  • Induces a decrease in calcium.
  • Produced by parafollicular cells (C cells) of the thyroid.
  • Small peptide (32 amino acids) with disulfide bridging.
  • Produced as a pre-hormone, stored in granules, released by exocytosis.
  • Basal level of secretion; increases when calcium levels increase.
  • Gastrointestinal hormones influence calcitonin secretion (priming for anticipated calcium influx).

Calcitonin Effects

  • Bone: Decreases movement of calcium from bone to extracellular fluids; inhibits osteoclasts.
  • Gastrointestinal Tract:
    • Decreases calcium absorption
  • Kidneys: Increases renal excretion of calcium.

Phosphate Balance

  • Calcitonin influences phosphate availability.
  • Excessive action of calcitonin can result in phosphate removal through renal excretion.

PTH and Calcitonin Together

  • Bone is the main storage of calcium.
  • Calcium level drops \rightarrow PTH secretion increases \rightarrow Calcium release from bone
  • Calcium level high \rightarrow stimulation of thyroid parafollicular cells occurs \rightarrow calcitonin released to facilitate calcium reabsorption in bones

Vitamin D

  • Sources: diet and ultraviolet (UV) light exposure to the skin, which stimulates cholesterol to become vitamin D3 (inactive form).
  • Vitamin D is produced in the skin/diet and modified in the liver and kidneys to produce an active compound (1,25-dihydroxyvitamin D3).
  • Modified form can be stored in adipose tissue because it's from cholesterol and is therefore lipophilic.
  • Parathyroid hormone (PTH) regulates activation of vitamin D in the kidneys.
  • Active vitamin D \rightarrow moves through the plasma membrane of the gastrointestinal tract where it can influence gene expression.
  • Activation of mechanisms which facilitate calcium retention or calcium pumping from the gastrointestinal tract through to circulation.

Vitamin D Synthesis and Activation

  • Sunlight \rightarrow Vitamin D3 formation \rightarrow liver enzymes and kidney enzymes modifies to change vitamin D confirmation \rightarrow resulting in active conformation \rightarrow facilitates calcium uptake in gastrointestinal tract

Abnormalities in Calcium Homeostasis: Hypocalcemia

  • Common in dogs/dairy cows, especially near parturition.
  • Mobilizing a lot of calcium for bone growth in fetus during pregnancy and also there is a drainage on lactation of calcium that binds milk proteins; calcium holds proteins in confirmation.
  • Clinical emergency but easily reversed with calcium supplementation (e.g., calcium phosphate infusion).